Placental ferroportin protein abundance is associated with neonatal erythropoietic activity and iron status in newborns at high risk for iron deficiency and anemia

Background: Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. Objectives: This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. Methods: Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 +/- 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 +/- 1.3 wk) and from 130 neonates born to 65 females (30.4 +/- 5.2 y) carrying multiples (delivery GA: 35.0 +/- 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). Results: FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: I3: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: I3: 0.20; 95% CI: 0.03, 0.18; hepcidin: I3: -0.06; 95% CI: - 0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (I3-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (I3: -0.02; 95% CI: -0.03, -0.003), EPO (I3: 0.07; 95% CI: 0.01, 0.14), and sTfR (I3: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (I3: 0.08, 95% CI: 0.02, 0.14), TBI (I3: 0.02; 95% CI: 0.009, 0.04), EPO (I3: -0.10; 95% CI: - 0.19, -0.01), sTfR (I3: -0.16: 95% CI: -0.27, -0.06), and hepcidin (I3: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). Conclusions: Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.